Previous review of the topic of insomnia

Briefly I pointed out that in some people there is a mutation of the gene that controls the circadian sleep rhythm. It is called the CRY1mutation. Some people have sleep disturbances from working night shifts. I mentioned the blue light of electronics that is produced by the TV screens or computer screens. The more you are exposed to it, the more it stimulates the brain to produce serotonin. This undermines the melatonin production, and as a result the person finds it extremely difficult to fall asleep. Children playing with i-phones, tablets or watching children’s programs on television can have sleep disturbances from the blue light. Blue has the frequency that over stimulates the brain and interferes with melatonin production. Drug and alcohol abuse can also interfere with the normal circadian sleep rhythm and cause insomnia.

Hormone factors of insomnia

For natural sleep to occur, we need melatonin which the pineal gland releases in the evening. It initiates and maintains sleep during the night. The natural opponent of melatonin is cortisol, the stress hormone, from the adrenal glands. Both hormones need to be in balance to allow you to sleep normally. Shortly before we wake up in the morning melatonin production goes down and cortisol production is up. Cortisol levels are low at night and high during the day. So it is cortisol that keeps us going throughout the day. But an excess of cortisol from chronic stress can also interfere with falling asleep and sleeping through the night.

Stress and insomnia

When we feel stressed, cortisol production goes way up. This has consequences regarding our sleep pattern. It can interfere with falling asleep, causes us to wake up from a deep sleep in the middle of the night and can give us problems falling asleep again. Chronic stress exposure leads to high cortisol production by the adrenal glands, which in turn will lower melatonin and cause sleep disturbances. Older people (above the age of 50) have very little melatonin production left, as there is an age-related decline of melatonin production. The melatonin production is highest in younger years and lowest in older age.

What to do when you are sleepless

There are several over-the-counter remedies, which in combination can be quite effective.

Melatonin for when you are sleepless

Melatonin (3 mg at bedtime) is a good start to see what it does for your sleeplessness. Taking a small amount of melatonin at bedtime we can re-establish the balance between cortisol and melatonin, which helps the circadian hormone rhythm and sleep pattern to come back. Some people wake up in the middle of the night and find it difficult to fall asleep again. If this happens at 3 AM, a good remedy at this time is to take another 3 mg of melatonin. Melatonin stays in the system for about 4 hours. Light during the day de-activates the effect, when light hits the retinas upon opening your eyes. You should not exceed 6 mg of total melatonin overnight. Otherwise it will interfere with the balance of cortisol and melatonin, lowering cortisol levels, which would rob you of energy during the day.

Phosphorylated serine (Seriphos)

A supplement that is freely available in the US (but not in Canada) consists of a simple amino acid. As this link shows (second item in the link) phosphorylated serine Seriphos) helps to down-regulate cortisol levels (lowering them). This means that melatonin gets the upper hand and you can sleep again.

The dosage for phosphorylated serine (Seriphos) varies from person to person, but will be in the range of 1000 mg to 3000 mg in the evening. After about 30 days the circadian rhythm may have recovered and you can stop the Seriphos. A one-day pause is required once a month for resetting the hormone receptors. Should you still have problems sleeping, you can continue with it for another month and pause again for a day. Seriphos has very few side effects.

Valerian root capsules

Another useful sleep aid is valerian root (as capsules). 500 mg to 1000 mg will help you to relax. It does not have the side effect of feeling groggy the next morning.

Other considerations when you are sleepless

Hormone problems like thyroid abnormalities (too much or too little thyroid hormones) are issues that your doctor has to investigate. Women in menopause often have sleep disturbances due to a lack of estrogen and progesterone. A knowledgeable healthcare professional is able to take care of that by prescribing bioidentical hormone creams.

When men approach andropause (the equivalent of menopause in women), they lose testosterone production. This can cause insomnia. The doctor can verify the hormone loss by a blood test. Replacement with either bioidentical testosterone cream or injections will rebalance testosterone levels. Insomnia may disappear. It is essential not to overdose testosterone, as this can also cause insomnia.

Sleep lab for when you are sleepless

When home remedies do not help, it may be time to check into one of the sleep labs to diagnose the kind of sleep disorder you are suffering from. Here is an overview what is happening there.

Essentially you get hooked up to monitors and are encouraged to just sleep as you would normally do. The physician in charge of the lab will later explain to you what the monitors showed, and tell you what type of sleep. According to the findings your doctor will recommend what measures are appropriate to remedy the situation.

Treatment for insomnia when over-the-counter remedies fail

Short acting benzodiazepams

When anxiety is not a problem, but only insomnia is (falling asleep or staying asleep) lorazepam 1 mg (Ativan) or temazepam 10 mg (Restoril) are shorter acting benzodiazepams that will help. It is not a permanent but a short “emergency break” for intermittent use, so that the GABA benzodiazepine receptors have time to recover. Otherwise, with continuous use tolerance would set in. This means higher and higher doses of the sleep medication would be necessary to achieve the same effect. Another non-benzodiazepine is Zolpidem 5 mg (Ambien). Even though this medication is not a benzodiazepine, it works on stimulating the same GABA benzodiazepine receptors.

Longer acting benzodiazepams combined with antidepressant Trazodone

For several years the combination of a small amount of the longer acting benzodiazepams, clonazepam (Rivotril) at 0.5 mg combined with a small amount of the anti-depressant trazodone (Oleptro or Desyrel) at 50 mg at bedtime has been has been in use quite successfully.

Trazodone, which is an antidepressant has a sleep cycle restoring effect at low doses and has less side effects, because it is used at ¼ the dose for a full-blown depression. Males are often complaining that it reduces their sex drive, and it may cause erectile dysfunction.

Clonazepam side effects

Rivotril was originally in use to control epileptic seizures and anxiety. The combination therapy for sleep disorders uses Rivotril at ¼ of the regular dose. Although it is good as a sleep aid, it has a long half-life and stays in the system well into the next day. This may present as sleepiness and cause falls in elderly patients because of clouded attention. Replacement by one of the medium long acting benzodiazepams could be the solution. A drug pause for 1 day will help to reset the GABA benzodiazepine receptors and prevent tolerance from happening. Knowing all those effects and side effects it is wiser to reserve the use of these medication strictly when everything else has failed!

When you are sleepless

Conclusion

As I mentioned before, you are not alone when you are sleepless. Insomnia can present as having problems to fall asleep, but it may present in others as a problem in the middle of the night waking up and having problems going back to sleep again.

I described non-conventional methods to help you to sleep using melatonin, Seriphos and valerian root capsules. If this fails, a sleep lab investigation may be necessary to get to the bottom of your insomnia problem. Physicians often prescribe short acting benzodiazepams like lorazepam (Ativan) and temazepam 10 mg (Restoril).

Other possibilities to treat insomnia

There are other possibilities to treat insomnia, with a combination of a low-dose antidepressant (trazodone, brand name Oleptro in the US) and low-dose anti-seizure and anti-anxiety drug clonazepam (Klonopin or Rivotril). Anxiety can often be a big component in insomnia and this treats both. On the other hand, anxiety is a separate problem, which needs professional treatment. There can be side effects of sleepiness from clonazepam and men complain of a lack of sex drive and erectile dysfunction from trazodone. Help is available when you are sleepless. But you need professional help to work on the problem and find the solution.

Some people look 10 years older than their stated age, and we often wonder: what causes premature aging? Accelerated or premature aging can have a multitude of underlying causes. I will list a few here:

1. Weakening hormones

Men go through andropause at around the age of 60 to 65 and women go through menopause around the age of 55 to 65. In both males and females it is the sex hormones that are missing around that age. If hormones replacement follows fairly quickly with bioidentical hormones, this will not affect the visual appearance that much. In contrast, if bioidentical hormones are not the therapeutic choice for hormone replacement, but synthetic ones, the hormones are not in balance, as synthetic hormones do not restore the hormonal balance. Nothing is gained, as the person will still age prematurely.

Synthetic versus bioidentical hormone replacement

In addition the synthetic hormones will cause heart attacks, strokes, clots, and cancer. Prescriptions for synthetic hormones are often the cause that the aging patient population gets these serious complications. Frequently physicians insist on using synthetic hormones from a “reputable” drug company to replace missing hormones. The reason this does not work is that a male has testosterone receptors. They need to be stimulated by bioidentical testosterone to restore all of his missing functions. Also, the same is true in menopausal females who need stimulation of their estrogen receptors and progesterone receptors. Consequently, only bioidentical hormones will return a postmenopausal woman back to normal. There is a perfect fit between the bioidentical replacement hormones and her hormone receptors. Using synthetic hormones is like trying to unlock a door with a key that does not have a perfect fit: you damage the lock!

2. Missing human growth hormone (HGH) and thyroid hormones

These hormones have a special place in aging.

Human growth hormone deficiency

First, HGH production is running out in many people at age 60. A person with HGH deficiency will have lower muscle mass and strength. Other symptoms are dry and thin skin, particularly at the back of the hands. Men are balding, and they loose interest in sex. There are difficulties concentrating and they may have “senior moments”, which are memory lapses. Often they are prone to depression and anxiety. A blood test will frequently show elevated triglycerides. A blood test (IGF-1) and a urine test exist which make it possible to look for HGH metabolites to assess whether a 40, 50 or 60 year-old person is producing enough HGH. Many may need replacement of HGH. This is administered by injection through a tiny needle into the skin, similar to a diabetic injecting insulin. This will bring back what was missing due to HGH deficiency.

Thyroid hormone deficiency

Thyroid hormones (T3 and T4) are other important factors that could make you look older prematurely. Your hair is getting thinner; your skin turns dry and pale. The nails may be getting brittle. When the outside half of the eyebrows is very thin or missing, this can be a sign of hypothyroidism. In a similar vein the skin in the face may be puffed up due to swelling of the layers under the skin (myxedema). It is important to diagnose hypothyroidism, which is common in the aging population. The physician needs to order a blood tests (TSH, T3 and T4). If TSH is above the upper limit, your physician needs to replace both T3 and T4 by tablets (I prefer Armour as the T3 and T4 is balanced).

3. Smoking

The lining of the airways absorb cigarette smoke. The chemicals circulate around in the blood and lead to aging of the skin. Chronic cigarette smoke exposure also melts away the subcutaneous tissue. The end result is a haggard look. The natural glow disappears from the skin and because of carbon monoxide binding to hemoglobin the skin color looks more greyish. In addition the blood vessels are narrowing or clogging. This means that the body cannot absorb nutrients as well, and cells are starving. There is only one remedy for this: quit smoking!

4. Overexposure to ultraviolet light

The radiation of UV light can penetrate deep into and under the skin. This makes the subcutaneous fat melt away. The largest UV exposure is in the facial area. As a result we see aging there. The end result is a sagging appearance of the face. This link has an image of a woman before and after a non-surgical facelift with stem cells and fatty tissue: Stem Cell Treatments That Are Currently Available – Medical Articles by Dr. Ray

In a surgical procedure the physician harvests mesenchymal stem cells from fatty tissue by liposuction. A cell separator separates the mesenchymal stem cells, the connective tissue and the fat cells. The connective tissue is discarded. Mesenchymal stem cells and fat cells are mixed and injected into the thinned subcutaneous fatty tissue until the person’s younger facial contour is back to normal. Typically this will last for 10 years or more.

5. Drugs and alcohol abuse

Both can lead to malnutrition with weight loss and loss of subcutaneous fatty tissue, which causes sagging breasts in women. In men “beer tits” are common. The reason for this is estrogen accumulation, as alcohol interferes with the elimination of estrogen in the liver. Alcohol is a general cell poison. It causes all of the cells to age prematurely. The more alcohol you drink, the faster you age. The skin develops wrinkles, loss of elasticity and collagen, redness and puffiness. In other words chronic alcohol abuse ages you prematurely. The only remedy for this is to quit drinking. Some of your skin vitality may come back. Our body has an amazing capability to heal itself!

6. Medical illnesses

Many medical illnesses like diabetes, mental illness (depression and schizophrenia), multiple sclerosis, inflammatory bowel disease; cancer and others make you look a lot older very fast.

I will briefly explain the reasons for this.

Diabetes

With diabetes type 2 the pancreas releases too much insulin after a meal with starches and sugar; think about a sweet muffin or a toast with jam. The extra insulin causes inflammation. This stimulates enzymes that break down elastin and collagen, leading to wrinkles and sagging skin.

Mental illness like depression and schizophrenia

We know from studies that depression leads to shortening of telomeres. This in turn causes cell death in the most rapidly dividing cells like in the skin and hair follicles. The end result is prematurely aged hair and skin. Schizophrenia also leads to premature shortening of the telomeres, which causes premature aging, mitochondrial dysfunction, inflammation and oxidative stress. The end result is that the person looks older than what their chronological age is.

Multiple sclerosis

It is sometimes difficult to discern in patients with MS what is normal aging and what is aging from the disease. This link gives some background on this. Many MS patients are anxious, and anxiety and stress by itself also leads to premature aging.

Inflammatory bowel disease

The chronic inflammation of either ulcerative colitis or Crohn’s disease can lead to premature aging. High doses of vitamin D3 and molecularly distilled fish oil can be useful to help treat the inflammation. Probiotics are also important to restore the bowel flora.

Cancer

Cancer leads to cachexia (excessive weight loss). There is also excessive inflammation, which leads to accelerated aging. The inflammation causes increased oxidative stress. This leads to tissue damage and DNA damage, which makes all cells more vulnerable to develop other cancers. Oxidative stress can substantially accelerate telomere shortening. As a result skin can become saggy, wrinkles develop and the person looks prematurely aged.

7. A chronic lack of physical activity

People who never exercise tend to get overweight and eventually obese. This leads to premature aging. Exercise would elongate telomeres, but inactivity shortens them. Obesity leads to increased oxidative stress and to DNA damage. Obesity also shortens telomeres. All of this leads to premature aging.

What Causes Premature Aging?

Conclusion

These are only a few examples of causes of accelerated aging. The key is to stick to a healthy, balanced diet (like the Mediterranean diet) and exercise regularly. Stop smoking (if you do), don’t take street drugs, and make sure you get enough sleep. Getting enough sleep helps your hormones regenerate overnight. The sympathetic overdrive from your daily activities is counterbalanced by the parasympathetic activities during sleep that causes relaxation. For hormone replacement you may have to see an anti-aging physician, a naturopath or integrative medicine physician. This may be your only chance to address any hormonal deficiencies. Conventional medicine does a very poor job of HRT (hormone replacement therapy) with synthetic hormones. Conventional practitioners want to treat you with synthetic hormones that will make you sick. Hormones for replacement have to be bioidentical! This way you will live 10 to 15 years longer, look younger and stay healthy.

Dr. Gary Huber recently gave a lecture on what’s new about testosterone. He presented his talk at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. It was entitled “Evolution of Testosterone – Dispelling Myths & Charting a Future”.

History of testosterone

There are some notable historic landmarks with respect to the discovery of testosterone.

1869: Dr. Charles Brown-Sequard suggested that the “feebleness of older men” was due to a lack of testosterone. He injected himself with testicular extracts from dogs and guinea pigs.

1912: The Danish physician Dr. Thorkild Rovsing transplanted the testicles of a young soldier killed in battle into an old man with gangrene. The gangrenous wound healed completely.

1918: Dr. Leo Stanley sampled fresh testicles from executed prisoners at the San Quentin Prison and transplanted them to prison inmates. Some regained their sexual potency.

1930’s: Professor Adolf Butenandt collected 25,000 liters of urine from willing policemen. He was able to isolate a breakdown product of testosterone, androsterone. Eventually he isolated both progesterone and testosterone. He received the Nobel prize for his work with sex hormones in 1939.

Historical detours and misguided opinions about testosterone

1935: Because natural hormones cannot be patented, Big Pharma came up with the idea of modifying testosterone by adding a methyl group at the 17-alpha position of testosterone. This new substance, 17 alpha-methyltestosterone, was a new compound. The FDA could patent it. Men liked it, because they could swallow this testosterone derivative as a pill. However, the liver changed 17 alpha-methyl-testosterone into 17 alpha-methyl-estradiol, a strong estrogenic compound. The body could not metabolize this testosterone compound too well. Shortly after introduction into patients it became evident that 17 alpha-methyl-testosterone caused liver cancers. This “testosterone equivalent” was on the market for 50 years before the FDA outlawed it because I caused liver cancer. It also caused suspicion among physicians about any testosterone replacement, even the bioidentical hormones that are safe.

Prostate cancer myths

Prostate cancer myth

Conventional medicine teaches (and I have believed this for many years) that testosterone would be the cause for prostate cancer. This was based on old observations by Dr. Huggins, a Canadian born surgeon who practiced in Chicago, that orchiectomy improved the survival of advanced prostate cancer patients a bit. Dr. Lee pointed out that Dr. Huggins neglected to realize that testicles make both testosterone and small amounts of estrogen. The belief that testosterone production was the culprit of prostate cancer led to the practice of physicians to do orchiectomies. This inadvertently removed the real cause of prostate cancer, an estrogen surplus. This improved the survival of these patients somewhat. Nowadays we have more sophisticated testing methods.

Estrogen causes prostate cancer, testosterone does not

Dr. Abraham Morgentaler (Ref. 1) has compiled a lot of evidence about the importance of testosterone in men. He proved, based on a lot of more modern references, that it is not testosterone that is the cause of prostate cancer. We know now that estrogen dominance is responsible for prostate cancer and that this develops as stated above because of the low testosterone and low progesterone during the male menopause (also called “andropause”).

It is important, when testosterone deficiency is present in an aging man, to replace the missing testosterone with bioidentical testosterone.

Some physicians still practice the old method of hormone depletion therapy in advanced prostate cancer cases. But Dr. Morgentaler and other researchers have shown that it is wrong to do hormone depletion therapy or orchiectomies.

10% absorption rule myth

For years there has been a persistent myth that the skin would only absorb 10% of testosterone. There was never any proof of this and newer studies showed that indeed the skin absorbs about 90% of testosterone.

Misleading science created myths

Unfortunately three key medical journals, JAMA, NEJM and PLOS ONE have published misleading studies. The content did not discuss physiology, mechanism of actions, appropriate dosing or true science. But they concluded that testosterone therapy was causing heart attacks and strokes. There was an outcry about this particular study in the medical community reflected in the demand to retract this misleading article.

Unfortunately there were more similar false “studies”. The problem with these was that the controls were wrong or they compared unequal groups that were not comparable. It is reminiscent of previous effort of the tobacco industry wanting to cover up that cigarette smoke causes lung cancer.

Testosterone replacement treats the cause of the deficiency

Here we have the problem that testosterone cures so many conditions for which the Pharma industry has many patented medicines that control the symptoms. But testosterone can actually treat the cause of the illness, testosterone deficiency, which leads to a cure of many other symptoms.

For a long time confusion plagued the older physician generation. But younger physicians are replacing the older generation and they treat testosterone deficiency with bioidentical testosterone in the proper dose.

Clinical observations about a lack of testosterone

As this paper shows, men investigated in the 1980’s were still having higher testosterone levels in older age. But in the 1990’s and more so in 2004 these values have declined even more. This fact coincides also with other studies, showing decreased sperm health and increased infertility. The reason for this is also a lack of testosterone!

Causation of low testosterone

Dr. Huber pointed out that many studies have pointed to a variety of causes for low testosterone levels in men.

BPA, toxins and pesticides

BPA, toxins and pesticides that occupy testosterone receptors and interfere with the hypothalamus/pituitary hormone function that stimulates the Leydig cells to produce testosterone.

The more stress, the less testosterone

The more stress men are under, the less testosterone production there is. Sleep deprivation below 5 hours per night leads to a significant lower testosterone production. Most testosterone production occurs during the sleep in the early morning hours.

Many references were provided that support these data. One paper reported that the risk of a heart attack climbs to 4 times the risk of normal, when the man sleeps less than 6 hours per night. As sleep hours lower, the risk for metabolic syndrome increases by 42% and this leads to heart attacks. Testosterone replacement can reverse this risk as it is a lack of testosterone production that caused the risk.

Link of low testosterone to cardiovascular disease

The literature is overwhelming that low testosterone has adverse effects on the cardiovascular system. To be more specific, the metabolic syndrome, heart disease (and strokes), diabetes and high blood pressure have their root in low testosterone.

Metabolic syndrome

Inflammation is mediated by cytokines such as IL-6. Dr. Huber mentioned one study where healthy men received IL-6. This promptly suppressed testosterone levels. He said that there are many cytokines that work in concert to suppress testosterone. One useful clinical test for inflammation is the C-reactive protein, which indicates whether or not inflammation is present in a person. Metabolic syndrome is common in obese patients. In a study CRP was found to be significantly associated with obesity. When CRP is high, testosterone levels are low. When the CRP level is high, there is a risk of getting the first heart attack.

Testosterone treatment and inflammation

On the other hand, when men with high inflammatory markers from low testosterone levels were replaced with testosterone, the tumor necrosis factor was reduced by 50%, IL1b by 37%, triglycerides by 11% and total cholesterol by 6%.

In the Moscow study a group of obese men with low testosterone levels were treated with testosterone injections. There was an impressive reduction of insulin (17%), CRP (35%) weight reduction of 4% and TNF-a reduction of 31% within 16 weeks.

Heart disease (and strokes)

Hardening of the arteries (medically called atherosclerosis) is due to chronic inflammation. Researchers developed a new heart attack/stroke specific biomarker. It is a ratio of oxidized LDL, divided by HDL. This has an odds ratio of 13.92 compared to a control without a risk for a heart attack or stroke.

Administration of testosterone hormone led to dilatation of coronary arteries. The Rotterdam study showed that low testosterone levels were associated with high risk for heart attacks and strokes, but that treatment with testosterone removed this risk. Testosterone increases AMP kinase for energy production in heart muscle cells, but also dilates coronary arteries for more blood supply to the heart.

Diabetes

Among men with diabetes 20-64% have low testosterone levels. In another study men with higher testosterone levels had a 42% lower diabetes risk. Testosterone levels are inversely related to body mass index and insulin resistance. Men with diabetes have lower testosterone levels than men who were not diabetic and were weight-matched. Most diabetics have high CRP values.

High blood pressure

Experience with androgen deprivation therapy for prostate cancer has shown that blood pressure gets elevated due to testosterone deficiency. Testosterone increases LDH, the protective subunit of cholesterol, and decreases LDL cholesterol and triglycerides. Testosterone also lowers inflammatory markers and reverses clotting factors making blood thinner. All of this leads to a widening of the arteries and lowering of blood pressure.

Treatment options for low testosterone

It is important to support the hypothalamic /pituitary/adrenal gland axis and remove other causes, such as stress and lack of sleep. Younger men can be stimulated in the pituitary gland through Clomiphene. Men older than 60 likely have true secondary hypogonadism and need testosterone replacement. Topical testosterone creams are available commercially or from compounding pharmacies. Injectable testosterone preparations that can be metabolized by the body are available. One such preparation is Delatestryl. A small dose (like 50 mg) is self-injected subcutaneously twice per week, which keeps the testosterone level stable. The last resort, if the creams or injections don’t work, is the use of testosterone pellets that a physician can implant under the skin.

What’s new about testosterone?

Conclusion

At a recent Anti-Aging conference in Las Vegas that I attended, Dr. Huber gave an overview of testosterone. There has been an objective reduction of testosterone levels in men since the 1980’s due to pollutants in our environment. Testosterone plays a key role for heart and brain function. It affects sex drive, fertility and potency. But it also prevents diabetes, high blood pressure and weight gain. On top of that it prevents prostate cancer and likely many other cancers. The key with low testosterone is to replace it to high normal levels. Blood levels should be measured every two months, when replacement has been instituted, in order to ensure adequate levels.